FDA Approves Ultragenyx's Fayuvi, First Gene Therapy for Sanfilippo Syndrome Type A

The U.S. Food and Drug Administration on September 17 approved Ultragenyx Pharmaceutical's Fayuvi (rebisufligene etisparvovec-hopf), a one-time gene therapy for children with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A, the agency announced. The FDA said it is the first treatment for the disease; until now, care was limited to managing symptoms.

MPS IIIA is a rare inherited disease that progressively damages the brain and nervous system, causing children to lose cognitive, language and other developmental abilities, according to the FDA. Children with the disease lack enough sulfamidase, an enzyme needed to break down a sugar molecule called heparan sulfate, which builds up in cells.

How Fayuvi works and the evidence

Fayuvi is given as a single intravenous infusion. It uses a modified, non-infectious adeno-associated virus serotype 9 (AAV9) to deliver a working copy of the SGSH gene into the patient's cells so they can make sulfamidase, the FDA said.

The agency evaluated the therapy in an open-label, single-arm, multicenter clinical study in children with MPS IIIA. The study measured mean changes in cognitive scores in patients aged 2 to 5. Fayuvi-treated patients maintained or improved cognitive function compared with an untreated historical control cohort, the FDA said, in contrast to the plateau and decline expected in the natural course of the disease.

Ultragenyx had applied for accelerated approval, but the agency granted full approval, MedCity News reported. Chief medical officer Eric Crombez said that reflects the strength of the clinical data, according to the report. The label states the therapy is indicated for children with preserved neurodevelopmental function, MedCity News reported, and chief executive Emil Kakkis said on a conference call that he expects the average age at treatment to be about 5.

"Today's approval of Fayuvi is a meaningful step forward — not only for these children and their families, but for the promise of gene therapy to address rare and devastating diseases where the need for safe and effective treatment is the most urgent," said Karim Mikhail, director of the FDA's Center for Biologics Evaluation and Research.

Safety, price and supply

The most common adverse reactions, reported in more than 5% of patients, were increased liver enzymes (AST), nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts, and increased amylase, according to the FDA. Warnings include the risk of thrombotic microangiopathy. As with other AAV-based gene therapies, there is a potential long-term risk that the inserted genetic material could integrate into the genome and lead to tumor development, the agency said. Patients receive corticosteroids starting one day before the infusion and continuing for at least eight weeks afterward.

Ultragenyx said Fayuvi will carry a wholesale price of $3.95 million before any rebates or discounts, MedCity News reported. The company estimates the lifetime cost of treating a Sanfilippo patient can top $8 million. The approval follows a 2025 rejection over manufacturing issues; the therapy will be made at an Ultragenyx site in Bedford, Massachusetts and by contractor Andelyn Biosciences in Ohio, with first shipments expected in 30 to 60 days, according to the report.

The approval came with a rare pediatric disease priority review voucher, which the company plans to sell. Fayuvi was originally developed by Abeona Therapeutics as ABO-102 and licensed to Ultragenyx in 2022, MedCity News reported. The FDA had granted it Orphan Drug, Fast Track and Breakthrough Therapy designations.